Antagonist of pituitary adenylate cyclase activating polypeptide suppresses prolactin secretion without changing the activity of dopamine neurons in lactating rats

Pituitary adenylate cyclase activating polypeptide (PACAP) is a relatively new neu ro peptide, a nd it has a potent stimulatory effect on adenylate cy clase activity in rat pituitary cells. However, the role of PACAP in the ph ysio logical control of prolactin (PRL) secretion is still unclear. in the present study, we investigated the physiological significance of endogenous PACAP on PRL secretion in lactating rats. On lactation days 7-8, pups were sepa rated from their mother rats for 5 h before the onset of suckling and PACAPs(6-38) (16 mug), a receptor antagonist, was injected through the lat eral ventricle cannula just after the removal of pups. The effects of PACAP (6-38) On PRL and oxytocin secretion, and on the activity of tyrosine hydro xylase (TH), were examined after the onset of suckling. Administration of P ACAP(6-38) inhibited PRL levels in response to suckling, but it did not aff ect the activity of TH, as measured by DOPA accumulation at 15 min after ad ministration of NSD 1015 (25.0 mg/kg), an L-aromatic amino acid decarboxyla se inhibitor, or the plasma concentrations of oxytocin in lactating rats. i njection of alpha -methyl-p-tyrosine (alpha -MT; 50 mg/kg), an inhibitor of dopamine synthesis, increased PRL levels, and suckling caused a further in crease in the plasma concentrations of PRL. An injection of PACAP(6-38) (i. c.v.) also inhibited the PRL response to suckling under dopamine depletion. These results suggest that endogenous PACAP acts as a neurotransmitter or neuromodulator within the hypothalamus and plays an important role for PRL secretion in lactating rats. Endogenous PACAP may regulate PRL secretion, p ossibly mediated by PRL-releasing factors such as vasoactive intestinal pol ypeptide or vasopressin. Copyright (C) 2001 S. Karger AG, Basel.